Methods of treating autoimmune microvascular disorders

Abstract

Methods of treating autoimmune microvascular conditions using diosmin or diosmetin are described, particularly the treatment of digital ulcers in systemic sclerosis.

The invention claimed is: 
     
       1. A method of treating an autoimmune microvascular disease in a subject in need thereof, comprising orally administering to said subject a formulation comprising as the sole active ingredient a therapeutically effective amount of diosmin or diosmetin, or a pharmaceutically acceptable salt thereof, or a combination thereof, for a therapeutically effective period of time. 
     
     
       2. A method of treating an ulcer in a subject with an autoimmune microvascular disease comprising orally administering to said subject a formulation comprising as the sole active ingredient a therapeutically effective amount of diosmin or diosmetin, or a pharmaceutically acceptable salt thereof, or a combination thereof, for a therapeutically effective period of time. 
     
     
       3. A method of treating an ulcer in a subject with systemic sclerosis comprising orally administering to said subject a formulation comprising as the sole active ingredient a therapeutically effective amount of diosmin or diosmetin, or a pharmaceutically acceptable salt thereof, or a combination thereof, for a therapeutically effective period of time. 
     
     
       4. A method of treating a digital ulcer in a subject with systemic sclerosis, comprising orally administering to said subject a formulation comprising as the sole active ingredient a therapeutically effective amount of diosmin or diosmetin, or a pharmaceutically acceptable salt thereof, or a combination thereof, for a therapeutically effective period of time. 
     
     
       5. The method of  claim 1  for treating an ulcer in a subject with an autoimmune microvascular disease. 
     
     
       6. The method of  claim 1  for treating an ulcer in a subject with systemic sclerosis. 
     
     
       7. The method of  claim 1  wherein said autoimmune vascular disease is selected from rheumatoid arthritis, systemic lupus erythematosus, Sjögren disease, systemic sclerosis, dermatomyositis, mixed connective tissue disease, leukoclastic vasculitis, antiphospholipid antibody syndrome, and paraproteinemias including cryoglobulinemia and cryofibrinogenemia. 
     
     
       8. The method of  claim 1 , for treating a digital ulcer in a patient with systemic sclerosis. 
     
     
       9. The method of  claim 1 , wherein the subject has microvasculitis. 
     
     
       10. The method of  claim 1 , wherein the subject has microvasculitis in terminal arterial vessels or capillaries. 
     
     
       11. The method of  claim 1 , wherein the subject has non-venous microvasculitis. 
     
     
       12. The method of  claim 1 , wherein the subject has non-venous microvasculitis in terminal arterial vessels or capillaries. 
     
     
       13. The method of  claim 1 , wherein said subject has a sclerotic condition selected from diffuse systemic sclerosis, limited systemic sclerosis, and morphea. 
     
     
       14. The method of  claim 1 , wherein said subject has CREST syndrome. 
     
     
       15. The method of  claim 1 , wherein said subject has one or more digital ulcers resulting from digital ischemia and secondary Raynaud's phenomenon. 
     
     
       16. The method of  claim 1 , wherein said subject has one or more digital ulcers due to ischemia from a combination of microvascular disease and actual capillary loss coupled with ischemia from vasospasm associated with secondary Raynaud's phenomenon. 
     
     
       17. The method of  claim 1 , wherein said therapeutically effective amount is from 300 to 5000 mg of diosmin or a pharmaceutically acceptable salt thereof, administered orally to the subject on a daily basis. 
     
     
       18. The method of  claim 1 , wherein said therapeutically effective amount is from 150 to 2500 mg of diosmetin, or a pharmaceutically acceptable salt thereof, administered orally to the subject on a daily basis. 
     
     
       19. The method of  claim 1 , wherein said therapeutically effective amount is from 400 to 2000 mg of diosmin, or a pharmaceutically acceptable salt thereof, administered orally to the subject on a daily basis. 
     
     
       20. The method of  claim 1 , wherein said therapeutically effective amount is from 200 to 1000 mg of diosmetin, or a pharmaceutically acceptable salt thereof, administered orally to the subject. 
     
     
       21. The method of  claim 1 , wherein said therapeutically effective amount is from 800 to 1200 mg of diosmin or a pharmaceutically acceptable salt thereof, administered orally to the subject on a daily basis. 
     
     
       22. The method of  claim 1 , wherein said therapeutically effective amount is from 400 to 600 mg of diosmetin, or a pharmaceutically acceptable salt thereof, administered orally to the subject on a daily basis.